Cells of the blood-brain and alveolar-capillary barriers share several structural and functional properties including the ability to take up and/or metabolize biogenic amines and prostaglandins. This metabolic capacity has been associated with endothelium of cerebral and pulmonary microvessels. The precise physiologic role of brain and lung endothelial cell metabolic function remains undefined, although it has been suggested that lung may act as a biochemical filter, regulating arterial levels of vasoactive hormones while cerebral clearance mechanisms may function to inactivate free amine and prostaglandin in the parenchyma. A detailed comparison of pulmonary and cerebral aminergic and autocoid activity in intact animals and in isolated microvessel should aid in interpreting the significance of endothelial cell function. Accordingly, the objectives of this study are: 1) to compare clearance of radiolabelled amines (5-hydroxytryptamine, norepinephrine) and prostaglandins (E and F series) from the cerebral circulation and cerebrospinal fluid using indicator dilution and ventriculocisternal perfusion techniques in intact dogs; 2) to determine alveolar clearance of aerosolized amines and prostaglandins deposited in an isolated perfused dog lobe and compare this clearance with known disposition of these substances within the pulmonary circulation; 3) to characterize the pharmacology and physiology of amine and prostaglandin disposition in isolated cerebral microvessels. These studies will compare the apparent transport kinetic parameters and drug sensitivity of hormone clearance in blood-brain and air-blood barriers as a function of the route of entry of material. Specific data on the contribution of endothelial cells to regional barrier function will be obtained in isolated microvessels. These studies will add to knowledge of endothelial cell physiology at both blood-brain and air-blood barriers and provide a basis for understanding altered endothelial cell function in pathologic conditions.